1. Field of the Invention
The present invention relates generally to the field of cancer treatment. More specifically, the present invention relates to a method of diagnosis and treatment for cancer such as breast cancer by combining techniques of tumor excision and margin ablation.
2. Description of the Related Art
Breast cancer will be diagnosed in approximately one in eight women in their lifetime and one in 30 will die of this disease. It is the leading cause of cancer deaths in women 40-55 years of age and the second leading cause of cancer deaths in women overall. Breast cancer does occur in males, but is much less common.
It is desirable and often necessary to perform procedures of detecting, sampling, and testing lesions and other abnormalities in the tissues of humans and other animals for pre-malignant conditions. This is particularly important in the diagnosis and treatment of patients with cancerous tumors. Typically, in the case of cancer, when a physician establishes by means of known procedures, i.e. palpation, mammography, x-ray, MRI, or ultrasound imaging, that suspicious circumstances exist, a biopsy is performed to determine whether the cells are cancerous. A biopsy is indicated if suspicious tissue is detected. Five out of six biopsies performed return benign indications.
Biopsy may be an open or percutaneous technique. Open biopsy removes the entire mass in an excisional biopsy or a part of the mass in an incisional biopsy. Percutaneous biopsy, on the other hand, usually is done with a needle-like instrument and may be either a fine needle aspiration (FNA) or a core biopsy. In fine needle aspiration biopsy, very small needles are used to obtain individual cells or clusters of cells for cytologic examination. The cells may be prepared such as in a Papanicolaou (Pap) smear. In core biopsy, as the term suggests, a core or fragment of tissue is obtained for histologic examination, which may be done via a frozen section or paraffin section. The chief difference between fine needle aspiration and core biopsy is the size of the actual tissue core taken. An imaging system having spectroscopic capabilities, such as the stereotactic guidance system described in U.S. Pat. No. 5,240,011, is employed to guide the extraction instrument to the lesion.
Depending on the procedure being performed, the suspicious lesion may be partially or completely removed. Visibility of the lesion by the imaging system may be hampered because of the distortion created by the extraction process itself as well as associated bleeding in the surrounding tissues. Although the lesion is removed and all fluids are continuously aspirated from the extraction site, it is likely that the process will “cloud” the lesion, thus impairing exact recognition of its margins. This makes it difficult to ensure that the entire lesion will be removed.
Often, the lesion is merely a calcification derived from tissue, which may be cancerous or precancerous, and, therefore, it is desirable to remove only a sample of the lesion rather than the entire lesion. Such a lesion actually serves to mark or define the location of adjacent abnormal tissue, so the physician does not wish to remove the entire lesion and, thereby, lose a critical means for later relocating the affected tissue. One of the benefits to the patient from core biopsy is that the mass of the tissue taken is small. However, oftentimes, either inadvertently or because the lesion is too small, the entire lesion is removed for evaluation, even though it is desirable to remove only a portion. Thus, if subsequent analysis indicates the tissue to be malignant, it is difficult for the physician to determine the precise location of the lesion in order to perform necessary additional procedures on adjacent potentially cancerous tissue.
A number of procedures and devices for marking and locating particular tissue locations are known in the prior art. For example, location wire guides, such as described in U.S. Pat. No. 5,221,269, are well known for locating lesions, particularly in the breast. The device comprises a tubular introducer needle and an attached wire guide that has at its distal end a helical coil configuration for locking into position about the targeted lesion.
The needle is introduced into the breast and guided to the lesion site using an imaging system of a known type, for example, x-ray, ultrasound or magnetic resonance imaging (MRI), at which time the helical coil at the distal end is deployed about the lesion. The needle may then be removed from the wire guide which remains in a locked position distally about the lesion for guiding a surgeon down the wire to the lesion site during subsequent surgery. While such a location system is effective, it is obviously intended and designed to be only temporary and is removed once the surgery or other procedure has been completed.
Other devices are known for marking external regions of a patient's skin. For example, U.S. Pat. No. 5,192,270 discloses a syringe that dispenses a colorant to give a visual indication on the surface of the point at which an injection has or will be given. Similarly, U.S. Pat. No. 5,147,307 discloses a device which has patterning elements for impressing a temporary mark in a patient's skin for guiding the location of an injection or the like. It is also known to tape or otherwise adhere a small metallic marker, e.g. a 3 millimeter diameter lead sphere, on the skin of a human breast in order to delineate the location of skin calcifications. Obviously, however, none of these approaches are useful for marking and delineating internal tissue abnormalities, such as lesions, tumors or margins.
A method of identifying and treating abnormal neoplastic tissue or pathogens within the body is described in U.S. Pat. No. 4,649,151. In this method a tumor-selective photosensitizing drug is introduced into a patient's body where it is cleared from normal tissue faster than it is cleared from abnormal tissue. After the drug clears normal tissue, but before it has cleared abnormal neoplastic tissue, the abnormal neoplastic tissue may be located by the luminescence of the drug within the abnormal tissue.
The fluorescence may be observed with low intensity light, some of which is within the drug's absorbency spectrum. Once detected, the tissue may be destroyed by further application of higher intensity light having a frequency within the absorbency spectrum of the drug. Of course, this method also is only a temporary means for marking the abnormal tissue. Additionally, once the abnormal tissue has been destroyed during treatment, the marker is destroyed as well.
It is also known to employ biocompatible dyes or stains to mark breast lesions. First, a syringe containing the colorant is guided to a detected lesion by an imaging system. Later, during the extraction procedure, the surgeon harvests a tissue sample from the stained tissue. However, while such staining techniques can be effective, it is difficult to precisely localize the stain. Also, the stains are difficult to detect using fluorescence imaging and may not be permanent.
In considering other treatment alternatives for breast cancer, surgeons treating both benign and malignant breast abnormalities have taken great interest in the advantages of percutaneous ablation over open surgical excision. Several small pilot trials attempting to treat fibroadenomas or small breast cancers with cryosurgery, laser ablation or radiofrequency have been reported. These ablative techniques employ freezing or indirect heat to ultimately induce cell death. Thermally-induced apoptosis impairs adequate pathologic assessment of tumor grade, lymphovascular invasion and biologic tumor markers, i.e., estrogen, progesterone and HER-2/neu, therefore necessitating a pre-ablative size assessment and histologic diagnosis via core bipsy.
Cryoablation creates an iceball in an elliptical fashion around the lesion with argon gas. The duration of the freezing cycle to create an adequately sized iceball is proportional to the size of the lesion. This cryoablative technique is visualized with real time ultrasound to monitor both the growth of the iceball, as well as its proximity to overlying skin or underlying pectoralis muscle. Currently the only FDA-approved indication for cryoablation is the treatment of a core biopsy proven fibroadenoma.
Using this technique 57 fibroadenomas were cryoablated in an office-based setting with only local anesthetic (1). This demonstrated that these lesions progressively shrink, eventually taking 12 months or more to completely resolve. The fact that a biopsy is obtained for pathologic concordance prior to any ablative process and that percutaneous excision via vacuum-assisted biopsy can be accomplished on the same visit in about 15 minutes seems to have pre-empted any ablative technique for benign purposes (2).
Multiple groups are studying the efficacy of cryotherapy in ablating small invasive carcinoma. It appears that the size of the cryoprobe may influence the ability to completely ablate different size cancers. In one study, 5 out of 16, i.e., 31%, 16 mm invasive breast cancers were ablated completely with a 3 mm probe (3). When patients with tumors ≧23 mm were treated, incomplete necrosis was seen in all excised specimens.
The cryoprobe has been used as an alternative method to needle localization to better obtain negative margins when excising non-palpable lesions (4). The cryoprobe was used to create an iceball that engulfed the non-palpable lesion plus an additional 5-10 mm of breast tissue surrounding the lesion. This technique made non-palpable lesions palpable, hence obviating the need for needle localization. By including a rim of adjacent normal breast tissue in the cryoprobe-generated iceball, the need for re-excision secondary to positive margins was reduced to 5.6%.
Laser ablation induces apoptosis by directing a specific wavelength of light into a narrow beam of high intensity light containing energy. This generated energy produces heat at the tip of the laser. Laser requires precise targeting with either MRI or stereotactic guidance to ablate a specific limited area. An MRI-guided laser was used in 12 patients to ablate completely breast tumors less than 3 cm prior to conventional surgical treatment (5). In three cases, simultaneous laser fibers were used to create a composite zone of ablation which successfully ablated these larger lesions. In 9 cases, portions of a larger mass were selected for ablation.
Stereotactic guidance has been examined during laser ablation of mammographic-detected small breast cancers for several years (6). The coordinates identifying the center of the lesion are stereotactically obtained and the laser fiber is inserted into this position using a 16 gauge needle. A multi-sensor thermal needle at the periphery of the lesion monitors tissue temperature. Tissue temperature of 50°-55° C. induces cellular death (7-8).
After implementing technical and procedural changes, the success rate for complete tumor ablation in two groups of 14 patients was 93% and 100%. The upper size criteria of a tumor or of a cluster of microcalcifications associated with ductal carcinoma in situ (DCIS) treated in these groups was ≦1.5 cm measured on ultrasound or diagnostic mammogram. The limitation on lesion size is due to the range of zone of ablation created by the laser. Typically the coagulative zone ranges 2.5-3.0 cm in diameter allowing for 0.5 cm negative margin circumferentially around the lesion (9).
Radiofrequency ablation is the most studied ablative technique. This technique utilizes alternating high-frequency current to agitate tissue ions between the prongs of a single probe. This agitation results in frictional heat to ultimately induce coagulative necrosis.
A multi-institutional study was conducted in which 20 patients with T1 breast carcinoma underwent intraoperative radiofrequency ablation followed by surgical excision (10). Complete ablation was found in 87% of patients using nicotinamide adenine dinucleotide staining. Incomplete ablation in four patients was thought due to the inability to adequately size the tumor with standard preoperative imaging or secondary to inappropriate targeting via ultrasound. In another study, both pre- and post-radiofrequency ablation with breast MRI used (11). The addition of MRI not only accurately assesses the local extent of disease preoperatively but also enables visualization of the zone of ablation, which differs from the intensity of residual carcinoma.
Recent trends in breast cancer treatment favor breast conservation surgery, with an emphasis on improved cosmetic results. However, prior to surgery, the patients must wait for pathology results of a biopsy before a final diagnosis can be given. Further waiting is required before the patients can be treated for removal of a malignant lesion. Moreover, breast conservation surgery via lumpectomy often results in some deformity and requires repeated surgery to establish a clear margin around the malignant lesion.
None of the presently available devices for excision adequately excise a margin, i.e., a tumor-free zone. Additionally, no work has been published on ablation of tumor bed margin after excision. Thus, there is a need in the art for improved, minimally-invasive methods of treating cancers or lesions resulting in established clear, negative margins. Specifically, the prior art is deficient in methods of treating breast cancer by excising the tumor and ablating the margin of the tumor in a minimally invasive manner. The present invention fulfills this long-standing need and desire in the art.